Cistična fibroza

Cystic fibrosis is the most common autosomal recessive genetic disease that limits lifespan in white populations. Hundreds of mutations have been discovered, with a huge range of clinical expressions. Identification of subjects with cystic fibrosis and carriers of the mutation enables genetic counseling and disease prevention. Early diagnosis, nowadays often through neonatal screening, allows early multidisciplinary approach with a positive impact on longevity and an increasing number of adult patients. As more patients live longer, the epidemiological indicators change and the number of complications on different organs increase. Standardization of care in cystic fibrosis centers with continuous multidisciplinary and longitudinal follow-up from pediatric age to adulthood contributes largely to better control of the disease and improving the quality of life.Cistična fibroza je najčešća nasljedna, autosomalno recesivna bolest koja utječe na dužinu života u bijeloj rasi. Danas je prepoznato više stotina mutacija uz veliku varijaciju ekspresije bolesti. Prepoznavanje bolesnika i nosilaca mutacije pruža mogućnost genskog savjetovanja i prevencije bolesti. Rano dijagnosticiranje, sve češće pomoću neonatalog probira, omogućuje rani multidisciplinarni terapijski pristup uz značajno produljenje životnog vijeka i sve većeg broja odraslih bolesnika. Dužinom životnog vijeka mijenjaju se epidemiološki pokazatelji bolesti te se uočava sve više komplikacija bolesti na drugim organskim sistemima. Osnivanje specijaliziranih centara za liječenje cistične fibroze s multidisciplinarnom longitudinalnom skrbi za bolesnike od pedijatrijske do odrasle dobi predstavlja daljnji doprinos kontroli bolesti i kvalitete života bolesnika

Lung transplantation in cystic fi brosis

Transplantacija pluća je sve češća terapijska mogućnost u završnom stadiju plućne bolesti. Jedna od najčešćih indikacija za transplantaciju danas je cistična fi broza, i to kako kod odraslih tako i u djece. Cistična fi broza nije samo bolest pluća nego je multisistemska bolest koja ima svoje posebnosti, o kojima treba voditi računa u izboru kandidata za transplantaciju. Transplantacija pluća danas je opcija za sve bolesnike s cističnom fi brozom i uznapredovanom plućnom bolešću koji ispunjavaju danas prihvatljive kriterije.The rate of lung transplantation, the most aggressive therapy available for end-stage lung disease, is increasing and cystic fi brosis is one of the most frequent indications for the procedure, both in children and adults. The burdens of comorbidities related to the underlying cystic fi brosis are important considerations and present unique challenges in candidates for lung transplantation. Lung transplantation is the fi nal treatment option for all patients with advanced cystic fi brosis lung disease if they meet the currently accepted inclusion criteria

Clinical presentations of cystic fi brosis in adulthood

Životni vijek bolesnika sa cističnom fi brozom stalno se produžuje zahvaljujući medicinskim spoznajama i njihovoj implementaciji u praksi, što utječe na porast broja odraslih bolesnika. Dužinom životnog vijeka mijenjaju se epidemiološki pokazatelji bolesti te se uočava sve više njenih komplikacija na drugim organskim sustavima. Stoga strategija za daljnje poboljšanje kakvoće života i životnog vijeka bolesnika sa cističnom fi brozom mora uključiti i preventivno djelovanje, kako bi se izbjegle, umanjile ili odgodile komplikacije u kasnijoj dobi.Medical care for individuals with cystic fi brosis has resulted in dramatic improvement in survival and subsequently a signifi cant change in the epidemiology of cystic fi brosis, bringing new challenges for patients and professionals. With an increasing number of patients reaching adult age, the impact of nutritional compromise and chronic infl ammation on diff erent organ systems has become increasingly manifest. The potential long term eff ect of medical interventions and therapies in early life, which aim to avoid, minimize or delay complications that occur later in life, should be considered as part of the strategies infl uencing the patient quality of life and long vitality

Malnutrition in cystic fi brosis – beyond pancreatic insuffi ciency

Neishranjenost u cističnoj fi brozi posljedica je nerazmjera između povećanih potreba za energijom, povećanih gubitaka, manjeg iskorištavanja hranjivih tvari s jedne strane i nedostatnog unosa hrane s druge. Vodeći uzrok maldigestije i malapsorpcije je insufi - cijencija pankreasa, no ni optimalna nadoknada enzima ne može ispraviti neishranjenost, jer ne djeluje na niz drugih čimbenika koji pridonose energetsko-prehrambenoj neravnoteži i trijadi infekcije, upale i opstrukcije u probavnom sustavu. Oni uključuju promijenjene karakteristike crijevnih sokova, disbiozu, nedostatak žučnih soli i neadekvatnu lipolizu, promjenu motiliteta, jetrenu bolest i drugo. Energetske potrebe veće su nego u zdravih osoba, zbog kronične infekcije i upale te dodatno rastu s propadanjem plućne funkcije. Dostatan unos hrane sprječavaju gastrointestinalne komplikacije, narušen tek, a često i psihosocijalni čimbenici. Važan je anticipirajući i aktivan stav liječnika i nutriciologa prema problemu uhranjenosti, čak i prije nego je ona narušena.Malnutrition in cystic fi brosis is a result of imbalance between increased energy requirement, increased losses and poorer nutrient utilization on the one hand, and inadequate food intake on the other hand. The most important cause of maldigestion and malabsorption is pancreatic insuffi ciency. However, even optimal enzyme replacement cannot correct malnutrition as it does not target many other causes adding to the nutritional imbalance and the pathophysiological triad of infection, infl ammation and obstruction. Contributing factors are abnormal intestinal juices, dysbiosis, bile salt abnormalities and altered lipolysis, altered motility, liver disease, etc. Energy requirements are increased in comparison to healthy subjects due to chronic infection and infl ammation, and additionally rise as pulmonary function deteriorates. Energy intake may be inadequate due to gastrointestinal complications, poor nutrient utilization, or psychosocial issues. An anticipatory and active attitude of gastroenterologists and nutritionists regarding nutritional problems is mandatory even before malnutrition emerges

Cystic Fibrosis and Bronchiectasis

Bronhiektazije čine heterogenu skupinu bolesti i poremećaja. U bijeloj rasi cistična fibroza najčešći je nasljedni uzrok bronhiektazija. Iznijete su osobitosti cistične fibroze kao multisistemske bolesti koja i u terapijskom pogledu traži složen pristup. Prikazane su okolnosti koje pogoduju razvoju bronhiektazija u cističnoj fibrozi. Iznosi se pregled terapijskih mjera. Liječenje plućnih komplikacija samo je dio postupaka koji su nužni u zbrinjavanju bolesnika s cističnom fibrozom i dio su prevencije i liječenja bronhiektazija.Bronchiectasis is caused by a heterogeneous group of diseases. Cystic fibrosis is the most common inherited cause of bronchiectasis in Caucasians. This paper describes the characteristics of cystic fibrosis as a complex disease involving many systems and requiring a multidisciplinary therapeutic approach. It also discusses the circumstances that predispose to the development of bronchiectasis, and provides an overview of treatments. The therapy of pulmonary manifestations is an important factor in preventing and treating bronchiectasis

Sindrom akutnog respiracijskog distresa u četvorogodišnjeg dječaka s dijabetičnom ketoacidozom - prikaz slučaja

Among many disease states as known initiators of acute respiratory distress syndrome (ARDS), diabetic ketoacidosis (DKA) is the rarest one. We present a 4-year-old boy with DKA as the first manifestation of insulin-dependent diabetes mellitus who developed ARDS, required tracheal intubation and mechanical ventilation, and survived without significant sequels. To improve survival of patients with ARDS as a complication of DKA, physicians should be aware of this rare pulmonary complication and its appropriate management.Među poznatim inicijatorima sindroma akutnog respiracijskog distresa (ARDS) dijabetična ketoacidoza (DKA) je najrjeđi. U ovom radu prikazujemo 4-godišnjeg dječaka s DKA kao prvom manifestacijom o inzulinu ovisne šećerne bolesti u kojega se razvio ARDS te je zahtijevao mehaničku ventilaciju i preživio bez značajnijih posljedica. Kako bi se unaprijedilo preživljenje bolesnika s ARDS kao komplikacijom DKA liječnici trebaju biti upoznati s ovom rijetkom plućnom komplikacijom i njezinim pravilnim liječenjem

Alfa-hormon koji stimulira melanocite smanjuje oštećenje sluznice debeloga crijeva u štakorskome modelu upalne bolesti crijeva

The aim of the study was to investigate the dose-dependent in vivo effect of alpha-melanocyte stimulating hormone (α- MSH) in a rat model of inflammatory bowel disease induced by 2,4,6-trinitrobenzene sulphonic acid (TNBS). Laboratory animals (male Wistar rats weighing 200–250 g) were given 3 doses of α- MSH (0.5 mg/kg, 1 mg/kg, 2 mg/kg) intraperitoneally 1 hour prior to inducing colitis with a TNBS enema. Control animals received saline solution i.p. Rats were sacrificed after 72 hours and the area of mucosal lesions, involving the distal 10 cm of colon, was determined in mm2 by means of image analysis software. α- MSH structure was analyzed by means of NMR spectroscopy. The area of colonic damage was significantly reduced following pretreatment with a single dose of 1 mg/kg α- MSH, as compared to control animals (p = 0.0147). Higher and lower doses had no significant effects. A single dose of 1 mg/kg α- MSH provided strong, statistically significant and pharmacologically relevant cytoprotection. The results point to α- MSH effectiveness in controlling inflammation and imply that further in vitro and in vivo experiments should be carried out to judge the importance and relevance of α- MSH in the control of inflammatory bowel disease. NMR data support a hairpin loop conformation of α- MSH in water solution, which includes conserved message sequence.Svrha istraživanja bila je kvantifikacija in vivo učinaka alfa-hormona koji stimulira melanocite (α- MSH) na štakorskome modelu upalne bolesti crijeva inducirane s 2,4,6-trinitrosulfonbenzenskom kiselinom (TNBS). Laboratorijskim životinjama (mužjaci Wistar soja štakora tjelesne mase 200–250 g) dane su tri doze α- MSH (0.5 mg/kg, 1 mg/kg i 2 mg/kg) intraperitonealno 1 sat prije indukcije kolitisa s TNBS klizmom. Kontrolne su životinje primile fiziološku otopinu intraperitonealno. Nakon 72 sata štakori su žrtvovani, te je pomoću programa za analizu slike procjenjena površina mukoznih lezija (mm2) unutar 10 distalnih centimetara kolona. Struktura α- MSH je analizirana uporabom NMR spektroskopije. Površina oštećenoga debeloga crijeva statisti- čki je značajno smanjena kod pretretmana s jednom dozom 1 mg/kg α- MSH, u odnosu na kontrolne životinje (p = 0.0147). Više i niže doze nisu imale značajne učinke. Pojedinačna doza od 1 mg/kg α- MSH uzrokovala je statistički značajnu i farmakološki relevantnu citoprotekciju. Rezultati ukazuju na učinkovitost _-MSH peptida u kontroliranju upale i upućuju na uporabu daljnjih in vitro i in vivo istraživanja kako bi se procijenio značaj i učinkovitost α- MSH u kontroli upalne bolesti crijeva. NMR mjerenja u vodenoj otopini podupiru pretpostavku o konformaciji _-MSH i njegove konzervirane sekvencije u obliku ukosnice

SIGNIFICANCE OF NEONATAL SCREENING FOR CYSTIC FIBROSIS

Cistična fibroza (CF) je autosomno recesivno nasljedna bolest i smatra se najčešćom smrtonosnom bolešću u bijele rase. Dijagnostički pristup bolesti temelji se na dijagnostičkom konsenzusu po kojem se sumnja na CF može ¬postaviti među ostalim i na osnovi pozitivnog nalaza novorođenačkog probira. Dok je u svijetu zadnjih godina sve više djece koja se otkrivaju u programu novorođenačkog probira, u Hrvatskoj se on ne provodi. Bolesnici u kojih se dijagnoza postavi nakon novorođenačkog probira imaju neke prednosti, rizike ali i nove probleme, te izazove za medicinsku struku s kojima se nismo susretali u dosadašnjoj praksi. Prednost probira najviše se očituje u boljoj uhranjenosti i boljem potencijalu kognitivnih funkcija te u izbjegavanju komplikacija koje su posljedica malnutricije. Prednost glede očuvanja plućne funkcije sadrži više kontroverza. Rano prepoznavanje bolesti često dovodi do ranog izlaganja bolesnika riziku ¬infekcija Pseudomonasom zbog odlaska u ustanove u kojima susreće druge bolesnike s CF. Poznavanje prednosti i rizika novorođenačkog probira na CF omogućuje procjenu njegove važnosti ne samo za bolesnika ili njegovu obitelji već i za čitavu zajednicu.Cystic fibrosis is among Caucasians the most common lethal autosomal recessive inherited disease. Diagnosis is based on meeting the criteria published as an expert consensus. Neonatal screening is one of the mentioned criteria. The number of children diagnosed with cystic fibrosis through neonatal screening is increasing throughout the world, but is not performed in Croatia. Early identification of these patients carries some advantages and some risks, posing new challenges for health workers. The most pronounced advantage is better growth and cognitive potentials for screened children, as well as less complications arising from malnutrition. Benefits regarding preservation of lung function are more controversial. Detection of patients through screening programs often means early exposure to Pseudomonas infections due to contacts with other CF patients in specialized centers. Recognizing potential advantages and risks of neonatal screening programs for CF brings new knowledge not only for individual patients and their families, but for the entire community

Met-Enkephalin Effects on Histamine-Induced Bronchoconstriction in Guinea Pigs

We investigated the effects of the neuropeptide met-enkephalin on histamine-induced bronhoconstriction in an experimental model of asthma. Classic Konzett and Rössler’s method of whole body plethysmography modified by Gjuriš, was applied in the study. This method represents a standard experimental model of bronchoconstriction, suitable for the evaluation of peptide effects on the histamine-induced bronchoconstriction. The results of the measurements implicate a dose-related modulatory effect of met-enkephalin on the bronchoconstrictor action of histamine. Met-enkephalin doses of 1 mg/kg and 10 mg/kg, respectively, caused statistically significant reduction of the histamine-induced bronchoconstriction. Estimated ED50 dose was 0.235 mg/kg. Further studies are needed to define practical and therapeutical use of the presented observations in respiratory pharmacology